This continuation application contains biomedical projects, education and health services proposals, and core units to support both components. We propose 7 biomedical D&F projects, 3 EEHS experiments, a biomedical core unit, a data analysis core, and an administrative unit. The current projects build upon our strengths, including a) expansion of our base of investigators and disciplines due largely to the current MAMDC, b) participation of established investigators with active research programs, c) inclusion of promising young investigators, d) solid research funding from sources outside the MAMDC, and e) effective interactions with a large community of individuals with multiple different ethnic backgrounds. The D&F proposals investigate mechanism of rheumatic diseases and therapies. They include analysis of structure of pathogenic rheumatoid factor subsets; a search for cryptic peptides in heat shock proteins that escape tolerance and activate arthritogenic T cells; study of the ability of glucocorticoids to exert anti-inflammatory effects via suppression of inducible prostaglandin synthase; identification of polymorphisms in the human IL-6 gene associated with SLE; development of a novel system in transgenic mice to test antigen-driven mutations in anti-DNA for mutations to pathogenic autoantibodies; an in situ analysis of cytokines, molecules that mediate inflammation, and cells that cause synovitis in collagen arthritis in rats and the influence of new therapies; and studies of osteogenic stem cells in normal, aged and glucocorticoid-treated mice. The EEHS experiments include a project to improve the self-management of gout through patient education and family member support, an analysis of the influence of severe RA on quality of life which compares homebound women who are Hispanic to non-Hispanic whites, and an analysis of the longterm outcomes of patients with RA who develop erosions during the first 2 years, using a consortium of community physicians who enter patients with early disease into one of several therapeutic algorithms. The biomedical core will synthesize peptides: the data core will facilitate study designs, data acquisition and analysis.